2. Academic Validation
  3. 89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake

89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake

  • Clin Cancer Res. 2019 Jun 15;25(12):3517-3527. doi: 10.1158/1078-0432.CCR-18-2918.
Kirsten L Moek 1,  Stijn J H Waaijer 1,  Iris C Kok 1,  Frans V Suurs 1,  Adrienne H Brouwers 2,  C Willemien Menke-van der Houven van Oordt 3,  Thijs T Wind 1,  Jourik A Gietema 1,  Carolien P Schröder 1,  Shekar V K Mahesh 2,  Annelies Jorritsma-Smit 4,  Marjolijn N Lub-de Hooge 4,  Rudolf S N Fehrmann 1,  Derk Jan A de Groot 1,  Elisabeth G E de Vries 5
Affiliations

Affiliations

  • 1 Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 2 Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 3 Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
  • 4 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 5 Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. e.g.e.de.vries@umcg.nl.
PMID: 30745297 DOI: 10.1158/1078-0432.CCR-18-2918
Abstract

Purpose: Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in 9 patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), an approximately 55 kDa bispecific T-cell engager (BiTE®) directed against carcinoembryonic antigen (CEA) on tumor cells and cluster of differentiation 3 (CD3) on T-cells.

Experimental design: 89Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment.

Results: Before AMG 211 treatment, the optimal imaging dose was 200-μg 89Zr-AMG 211 + 1,800-μg cold AMG 211. At 3 hours, the highest blood pool standardized uptake value (SUV)mean was 4.0, and tracer serum half-life was 3.3 hours. CD3-mediated uptake was clearly observed in CD3-rich lymphoid tissues including spleen and bone marrow (SUVmean 3.2 and 1.8, respectively), and the SUVmean decreased more slowly than in Other healthy tissues. 89Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUVmax of 4.0 [interquartile range (IQR) 2.7-4.4] at 3 hours using the optimal imaging dose. The tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment, tracer was present in the blood pool, whereas tumor lesions were not visualized, possibly reflecting target saturation.

Conclusions: This first-in-human study shows high, specific 89Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intraindividual heterogeneous tumor uptake.

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